© 2013 Wichtig Editore - ISSN 0391-3988 Int J Artif Organs ( 2013; : 11) 762-774 36 762 Development and analysis of semi-interpenetrating polymer networks for brain injection in neurodegenerative disorders Marta Tunesi 1, Sara Batelli 2 , Serena Rodilossi 2 , Teresa Russo 3 , Annalisa Grimaldi 4 , Gianluigi Forloni 2 , Luigi Ambrosio 3 , Alberto Cigada 1, Antonio Gloria 3 , Diego Albani 2 , Carmen Giordano 1, 1 Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di Milano and Unità di Ricerca Consorzio INSTM, Politecnico di Milano, Milan - Italy 2 Department of Neuroscience, IRCCS – Istituto di Ricerche Farmacologiche “Mario Negri”, Milan - Italy 3 Institute of Composite and Biomedical Materials, National Research Council of Italy, Naples - Italy 4 Department of Structural and Functional Biology, University of Insubria, Varese - Italy ORIGINAL ARTICLE DOI: 10.5301/ijao.5000282 INTRODUCTION Alzheimer’s (AD) and Parkinson’s diseases (PD) are severe neurodegenerative disorders strongly linked with aging. The hippocampus and the entorhinal cortex are the major brain areas showing the neuropathological lesions of AD, while in PD the dopaminergic neurons of the substantia nigra are the most affected, leading to a deficiency of do- pamine in the striatum. Both diseases significantly impair the quality of life for patients and their families and their Purpose: Our aim was to assess the use of injectable, biocompatible and resorbable, hydrogel-based tools for innovative therapies against brain-related neurodegenerative disorders like Alzheimer’s (AD) and Parkinson’s (PD) diseases. Methods: Two compositions of semi-interpenetrating polymer networks (semi-IPNs) based on col- lagen and poly(ethylene glycol) (PEG) were investigated. We examined their viscoelastic properties, flow behavior, functional injectability, as well as in vitro biocompatibility with SH-SY5Y human neuro- blastoma cells and murine primary neurons. We also evaluated the in vivo biological performance after subcutaneous and brain injection in mice. Results: The selected semi-IPNs showed a gel-like behavior and were injectable through a 30 G needle, with the maximum load ranging from 3.0 to 3.9 N. In vitro results showed that immortalized cells kept their proliferative potential and neurons maintained their viability after embedding in both materials, with better performances for the gel with the higher collagen content. For both semi-IPNs, after subcutaneous injection, the inflammatory response was negligible; after brain injection, the tissue did not show any signs of damage or degeneration. Conclusions: The results suggest that the selected semi-IPNs not only represent a proper environ- ment for cells, but also, once injected in vivo, do not induce damage/inflammation in the surrounding brain tissue. These findings represent a crucial starting point for the development of minimally invasive and injectable hydrogel-based tools for innovative drug/cell-based therapeutic strategies against AD, PD, or other severe brain-related neurodegenerative pathologies. Keywords: Brain, Neurodegenerative diseases, Hydrogels, Semi-interpenetrating polymer networks Accepted: October 31, 2013